A randomized controlled trial of smell training and trigeminal nerve stimulation in the treatment of COVID-related persistent smell loss

嗅觉训练和三叉神经刺激治疗新冠病毒相关持续性嗅觉丧失的随机对照试验

• 批准号: 10718703
• 负责人: Bashar W Badran
• 金额: $ 63.8万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10718703
• 关键词: 2019-nCoV; Acceleration; Address; Adult; Aftercare; Anosmia; Area; Attention; Brain; COVID-19; COVID-19 associated anosmia; Cognition; Cognitive; Communication; Detection; Development; Dropout; Drowsiness; Electric Stimulation; Etiology; Evidence based intervention; Evidence based practice; Evidence based treatment; Functional disorder; Healthcare; Home; Human; Impaired cognition; Impairment; Infection; Intervention; Investigation; Long COVID; Mental Health; Methods; Moods; National Institute on Deafness and Other Communication Disorders; Natural regeneration; Neurons; Pain Free; Paraosmias; Psychophysics; Publishing; Qualifying; Randomized, Controlled Trials; Recovery; Research; Science; Sensory; Sleep; Smell Perception; Speed; Strategic Planning; Symptoms; Taste Perception; Training; Treatment Efficacy; Trigeminal System; Trigeminal nerve structure; Work; cognitive function; combinatorial; coronavirus disease; coronavirus treatment; design; efficacy evaluation; executive function; hyposmia; improved; improved outcome; neuropsychiatric disorder; neuropsychiatric symptom; neuroregulation; non-compliance; noninvasive brain stimulation; novel; physical conditioning; post-COVID-19; response; sleep quality; standard of care; symptomatology

ABSTRACT COVID exposed the critical need for new and improved treatment interventions for chemosensory (i.e. smell and taste) dysfunction. Evidence indicates that COVID-related smell loss (SL) often endures well past recovery of the initial infection and is highly associated with other long COVID neuropsychiatric symptoms including impairments in mood, sleep, and cognition. To date, there are few interventions available to treat COVID-related persistent SL and its related impairments. While smell/olfactory training (ST) has emerged as a widely prescribed, front-line treatment for COVID-related persistent SL, rigorous study is required to determine its efficacy in long COVID. Moreover, given that ST is a lengthy treatment, requiring 12 weeks or longer of training, and is associated with slow improvement, non-compliance, drop-out, and modest effect size, additional study of adjunctive methods to improve its efficacy and speed of recovery are warranted. Here we propose the first study to investigate combinatorial trigeminal nerve stimulation (TNS) and ST in the treatment of post-COVID persistent SL and associated deficits in mood, sleep and cognitive impairment. Our previous work suggests that TNS, an easy-to-use and very safe form of non-invasive brain stimulation, increases olfactory sensitivity and has the potential to improve other symptoms of long COVID including mood, daytime sleepiness, and attention. Therefore, we will conduct a larger at-home, randomized, controlled trial of ST and determine whether TNS enhances the effects of ST in adults with COVID-related persistent SL. Our primary objectives are 1) to determine the efficacy of ST, compared to any natural gain in function, on olfactory-specific deficits (active ST versus sham ST), 2) to determine the TNS-enhanced effects of ST on olfactory-specific deficits (active TNS+ST versus active ST), and 3) to determine if TNS+ST, compared to ST, is also more efficacious in the treatment of other impairments (i.e. mood, sleep, and cognitive) associated with both SL and long COVID. While this research is focused on COVID-related persistent SL, the results will provide the necessary information to extend the study and use of ST and TNS to address wider chemosensory dysfunction. This line of investigation has the potential to make a substantial impact on how chemosensory dysfunction is treated and in turn significantly improve the current standard of care.

抽象的 COVID暴露了对化学感觉的新的和改进治疗干预措施的关键需求（即气味和 口味）功能障碍。证据表明与共同相关的气味损失（SL）通常会忍受过去的恢复 初始感染，并与其他长期相互共同的神经精神症状高度相关 情绪，睡眠和认知障碍。迄今为止，很少有干预措施可以治疗相关相关 持续的SL及其相关的障碍。虽然气味/嗅觉训练（ST）已成为广泛的 规定的，用于共同相关的持续SL的前线治疗需要严格的研究才能确定其 长期共同的功效。此外，考虑到ST是一种漫长的治疗，需要12周或更长的培训， 并且与缓慢的改善，不合规，辍学和适度的效果大小相关，对 必须采用提高其疗效和恢复速度的辅助方法。在这里，我们提出了第一项研究 研究联合三叉神经刺激（TNS）和ST在旋转后持续的治疗中 SL和相关的情绪缺陷，睡眠和认知障碍。我们以前的工作表明TNS， 易于使用和非常安全的非侵入性脑刺激形式，增加了嗅觉敏感性，并具有 潜力改善长期相互交射的其他症状，包括情绪，白天嗜睡和注意力。 因此，我们将进行较大的家用，随机，对照试验的ST，并确定TNS是否 增强与共同相关持续SL的成年人中ST的影响。我们的主要目标是1）确定 与嗅觉特异性缺陷相比，ST的功效与功能的任何自然增益相比 ST），2）确定ST对嗅觉特异性缺陷的TNS增强效应（主动TNS+ST与Active ST）和3）确定与ST相比TNS+ST是否在治疗其他方面也更有效 障碍（即情绪，睡眠和认知）与SL和长期相关。虽然这项研究是 该结果专注于与共同相关的持续SL，将提供必要的信息来扩展研究 并使用ST和TNS来解决更广泛的化学感应功能障碍。这种调查有潜力 为了对如何治疗化学感应功能障碍产生重大影响，然后显着改善 当前的护理标准。